Researchers Discover Gene that Elicits Antibody Response

A research team led by the La Jolla Institute for Allergy & Immunology report that the Bcl6 gene triggers the body to produce disease-fighting antibodies. Their research showed that turning on this gene produced more CD4 T-helper cells, which subsequently tell the B cells to produce antibodies.

The finding is published online in Science in a paper titled “Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper (TFH) cell differentiation."

It has been well established that antibody production is a multistep process that involves interactions between several cellular players, key among them CD4 helper T cells. “For many years, we in the scientific community thought that one of the four varieties of CD4 helper type 2 cells (known as TH-2 cells) triggered the antibody process,” explains the La Jolla Institute’s Shane Crotty, Ph.D., lead scientist on the team, which also included researchers from Yale University. “But about 10 years ago scientists realized this was incorrect and that there must exist a fifth variety of CD4 helper T cell that initiated antibody production. It was named TFH.”

Dr. Crotty’s team set out to understand the inner workings of the TFH pathway. “We discovered that the Bcl6 gene was like an on and off switch, or master regulator, in this process. In a series of experiments, we showed that if you turn on this gene, you get more CD4 T-helper cells (the TFH type), and it’s those cells that are telling the B cells to produce antibodies.”

Dr. Crotty’s group tested the finding by using a cellular mechanism to turn off the Bcl6 gene. Turning off the gene stopped the production of the TFH cells. “Without this genetic trigger, no TFH cells were produced and consequently no antibodies.” The researchers also found that the more TFH cells produced, the greater the antibody response. The Yale researchers who were part of the team were also able to duplicate these results.